The research program is to continue studies on the mechanism of initiation of insulin release by glucose and the role of the microtubular-microfilament system in insulin secretion. An in vitro model has been developed for studies on alloxan inhibition of glucose-induced insulin release from perifused rat islets.. Studies are in progress using alloxan as a possible probe for glucoreceptors on the beta cell membrane. The protective action of glucose and other agents on alloxan inhibition of secretion and the effect of these agents on hexose transport and insulin secretion are being determined. Studies are in progress on the transport of these protective agents into isolated islets as well as studies on the possible binding and/or transport of alloxan. Methods are being developed for the isolation of a plasma membrane fraction from isolated rat islets for studies on the site of action of alloxan and possible binding of glucose and other agents. Studies on the role of the microtubular-microfilament system in beta cell secretion and changes in the ratio of microtubulin to intact microtubules in isolated islets under different experimental conditions will be continued. In vitro studies on the secretion of human pancreatic polypeptide are in progress. BIBLIOGRAPHIC REFERENCES: McDaniel, M., Roth, C., Fink, J., Fyfe, G., and Lacy, P.E.: Effects of cytochalasins B and D on alloxan inhibition of insulin release. B.B.R.C. 66: 1089-1096, 1975. Lacy, P.E., McDaniel, M.L., Fink, C.J. and Roth, C.: Effect of methylxanthines on alloxan inhibition of insulin release. Diabetologia 11: 501-507,1975.